Beta-3 agonist approved for OAB
If you remember only beta-1 and beta-2 receptors, it’s time to catch up.
A new once-daily treatment for overactive bladder (OAB) with a novel mechanism of action—beta-3 agonist—has been approved by FDA. Mirabegron (Myrbetriq—Astellas) relaxes bladder muscle through beta-3 stimulation and is approved for treatment of OAB in adults with symptoms of urge urinary incontinence, urgency, and urinary frequency.
In recent years, the urothelium has emerged as a new target for management of OAB. Beta-1, -2, and -3 receptors are located in the human urothelium and detrusor muscle, but the beta-3 subtype predominates. Mirabegron targets beta-3 receptors, decreasing the frequency of rhythmic bladder contractions during the filling phase. This increases bladder capacity and improves symptoms in patients with OAB.
OAB is a urologic disorder characterized by bothersome symptoms such as urgency, increased voiding frequency, urge incontinence, and/or nocturia. Most patients are extremely distressed by these symptoms and find their quality of life decreased.
Both nonpharmacologic and pharmacologic therapies are used in treatment. Lifestyle modifications such as pelvic floor exercises and bladder training are are used alone or in conjunction with antimuscarinic agents. Use of antimuscarinic agent is limited by their adverse effects, including dry mouth, blurred vision, and urinary retention. Many patients are unable to tolerate therapy, and adherence rates drop.
New agents with alternative mechanisms of action are clearly needed in the management of OAB.
Clinical efficacy, safety
Approval of mirabegron was based on data from three double-blind, placebo-controlled, multicenter clinical trials. In all, 4,116 patients with OAB were randomly assigned to take mirabegron at doses of 25, 50, or 100 mg, an active control, or placebo once daily for 12 weeks.
Patients given mirabegron 25 or 50 mg had fewer urinations and wetting accidents in a 24-hour period. In addition, patients treated with the 50-mg dose expelled a greater amount of urine, demonstrating the drug’s effectiveness in improving the storage capacity of the bladder.
The most common adverse events with mirabegron were elevations in blood pressure, nasopharyngitis, urinary tract infection, constipation, fatigue, tachycardia, and abdominal pain. There are no contraindications to using mirabegron, and the labeling has minimal warnings or precautions for use of this agent (see sidebar).
Place in therapy
Overall, mirabegron is a welcome addition for the management of OAB. Most patients have used antimuscarinic agents, and their adverse effects result in high treatment discontinuation rates.
The new drug is more expensive than currently available antimuscarinic agents, most of which are available in generic form. The risk–benefit profile of mirabegron must account for this difference. Mirabegron may be a good initial treatment option for older patients, as dry mouth tends to be a problem in this patient population. In addition, for patients with Alzheimer disease, prescribers now have an option to control OAB symptoms without worrying about potential adverse cognitive effects and drug interactions with cholinergic agents used to manage that disease, as occurs with the antimuscarinic agents. Another consideration is that the long-term cardiovascular safety of mirabegron is unknown, and some clinicians may therefore choose to use this agent cautiously in patients with known heart and vascular problems.
Drug class: Beta-3 adrenergic agonist
Indication: Treatment of overactive bladder (OAB) in adults
Dosage: 25 mg once daily with or without food as a starting dose; after 8 weeks of therapy the dose may be increased to 50 mg once daily
- The recommended daily dose should not exceed 25 mg/d in patients with severe renal impairment (creatinine clearance 15–29 mL/min) or moderate hepatic impairment (Child–Pugh Class B). Treatment with mirabegron is not recommended for patients with end-stage renal disease or in those with severe hepatic impairment (Child–Pugh Class C).
Of note: Because of its hypertensive properties, mirabegron should not be used in patients with severe uncontrolled hypertension (systolic blood pressure of 180 mm Hg or more and/or diastolic blood pressure of 110 mm Hg or more).
- Mirabegron should be administered with caution in patients with bladder outlet obstruction and in those taking antimuscarinic medications for OAB, as increased urinary retention may occur.
- Mirabegron, a moderate cytochrome P450 (CYP)2D6 inhibitor, may interact with drugs that are CYP2D6 substrates. Dosage adjustments of drugs metabolized by this enzyme may be needed.
Emphasize the need for periodic monitoring of blood pressure in patients taking mirabegron. Potential adverse effects of therapy include infrequent urinary tract infections, increased heart rate, and various gastrointestinal effects. Astellas has developed a patient information leaflet for distribution to patients.